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Current Oncology (Toronto, Ont.) Feb 2021Improving therapeutic strategies for extensive-stage small cell lung cancer (ES-SCLC) remains a challenge. To date, no reports have directly compared the efficacy and... (Meta-Analysis)
Meta-Analysis Review
Comparative Efficacy and Safety of Immunotherapeutic Regimens with PD-1/PD-L1 Inhibitors for Previously Untreated Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.
Improving therapeutic strategies for extensive-stage small cell lung cancer (ES-SCLC) remains a challenge. To date, no reports have directly compared the efficacy and safety of immune checkpoint inhibitors plus platinum-etoposide (ICIs+EP) with platinum-irinotecan (IP) or directly compared different ICIs+EP for previously untreated ES-SCLC. This study used a Bayesian approach for network meta-analysis to compare efficacy and safety between ICIs+EP and IP and between each pair of three ICIs+EP. The six treatment arms were: pembrolizumab plus platinum-etoposide (Pem+EP), durvalumab plus platinum-etoposide (Dur+EP), atezolizumab plus platinum-etoposide (Atz+EP), platinum-amrubicin (AP), IP, and platinum-etoposide (EP). No significant differences in overall survival were observed between ICIs+EP and IP and between each pair of three ICIs+EP. The incidence of ≥grade 3 adverse events (G3-AEs) was significantly higher in ICIs+EP than IP, whereas no significant difference was found in G3-AEs between each pair of three ICIs+EP. The incidence of ≥grade 3 neutropenia and thrombocytopenia was significantly higher in ICIs+EP than IP, whereas the incidence of ≥grade 3 diarrhea was significantly lower in ICIs+EP than IP. These findings will help clinicians better select treatment strategies for ES-SCLC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Lung Neoplasms; Network Meta-Analysis; Programmed Cell Death 1 Receptor; Small Cell Lung Carcinoma
PubMed: 33673470
DOI: 10.3390/curroncol28020106 -
Annals of Oncology : Official Journal... May 2021Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated SCLC.
PATIENTS AND METHODS
CheckMate 331 is a randomized, open-label, phase III trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line, platinum-based chemotherapy were randomized 1 : 1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS).
RESULTS
Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy [median OS, 7.5 versus 8.4 months; hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.72-1.04; P = 0.11]. A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab versus chemotherapy) was similar in patients with programmed death-ligand 1 combined positive score ≥1% versus <1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%.
CONCLUSION
Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Lung Neoplasms; Neoplasm Recurrence, Local; Nivolumab; Progression-Free Survival; Small Cell Lung Carcinoma
PubMed: 33539946
DOI: 10.1016/j.annonc.2021.01.071 -
Therapeutic Advances in Medical Oncology 2020Our goal was to organize the data from randomized controlled trials that evaluated first-line chemotherapy for chemo-naïve extensive disease small-cell lung cancer...
BACKGROUND
Our goal was to organize the data from randomized controlled trials that evaluated first-line chemotherapy for chemo-naïve extensive disease small-cell lung cancer (ED-SCLC).
METHODS
The protocol following PRISMA methodology was submitted as PROSPERO 154049. We included individually randomized trials comparing two or more chemotherapy regimens as the first-line treatment for chemo-naïve ED-SCLC regardless of the age, sex, performance status, co-morbidities, and organ functions written in the English language since 2000. Molecular targeted agents and immune checkpoint inhibitors were considered chemotherapy along with cytotoxic medications. We pooled the logarithm of hazard ratio (HR) and its standard error using the frequentist weighted least squares approach random-model network meta-analysis.
RESULTS
A total of 46 eligible trials that involved 11,987 patients were included. The primary endpoint, HR of overall survival (OS, HRos) of the selected comparisons was as follows: carboplatin+amrubicin (HRos 0.56, 95% confidence interval (CI) 0.33-0.96), carboplatin+etoposide+atezolizumab (HRos 0.70, 95% CI 0.53-0.92), and carboplatin+irinotecan (HRos 0.73, 95% CI 0.58-0.91) were compared with carboplatin+etoposide. The carboplatin+etoposide+atezolizumab regimen was compared with carboplatin+irinotecan (HRos 0.97, 95% CI 0.68-1.37) and cisplatin+irinotecan regimen (HRos 0.87, 95% CI 0.58-1.31). "Selective carboplatin or cisplatin (CBDCA/CDDP)"+etoposide+durvalumab was compared with CBDCA/CDDP+etoposide (HRos 0.73, 95% CI 0.59-0.91). Platinum+etoposide+durvalumab was compared with platinum+irinotecan (HRos 0.88, 95% CI 0.67-1.15). Cumulative meta-analysis suggested that platinum+irinotecan was associated with better OS than platinum+etoposide as of 2010 through 40 out of 46 trials in our review that used platinum+etoposide as a reference regimen.
CONCLUSION
Patients treated with carboplatin+amrubicin, carboplatin+etoposide+atezolizumab, CBDCA/CDDP+etoposide+durvalumab, and platinum+irinotecan showed better HRos than those treated with platinum+etoposide, one of the standard regimens.
PubMed: 33403010
DOI: 10.1177/1758835920965841 -
Journal of Thoracic Disease Oct 2020Systemic treatment in small cell lung carcinoma has been a challenge for oncologists for decades. The high propensity for recurrence is usually due to distant... (Review)
Review
Systemic treatment in small cell lung carcinoma has been a challenge for oncologists for decades. The high propensity for recurrence is usually due to distant metastasis, which makes systemic treatment an essential component of treatment in small cell lung carcinoma. The regimen of cisplatin and etoposide (established in the mid-1980's) concurrently with thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) remains the standard of care in limited stage disease. Despite numerous trials, this regimen has not been improved upon. The standard combination regimen of cisplatin and etoposide has been compared to alternative platinum-containing regimens with drugs like epirubicin, irinotecan, paclitaxel, topotecan, pemetrexed, amrubicin and belotecan. Non-platinum containing regimens like ifosfamide and etoposide have also been tested. Attempts to intensify therapy have included the addition of a third drug like paclitaxel, ifosfamide, tirapazamine, tamoxifen, and thalidomide. Maintenance therapy following induction with chemotherapy, vandetanib and interferon-alpha have also been attempted. Molecularly directed targeted therapies and immunotherapeutic agents are areas of active research. In this review, we discuss the various systemic therapy options in limited stage small cell lung carcinoma, from the historical regimens to the modern-day therapy and promising areas of research. We also discuss the role of growth factors, the optimal number of chemotherapy cycles, the use of prognostic and predictive factors, the optimal timing of chemotherapy and the treatment of special populations of patients including older patients, and patients with comorbidities.
PubMed: 33209466
DOI: 10.21037/jtd-2019-sclc-11 -
Journal of Thoracic Disease Oct 2020Nearly all patients with extensive-stage small-cell lung cancer (ES-SCLC) relapse following first-line etoposide plus platinum (EP) with or without immune checkpoint... (Review)
Review
Nearly all patients with extensive-stage small-cell lung cancer (ES-SCLC) relapse following first-line etoposide plus platinum (EP) with or without immune checkpoint inhibition. Topotecan and amrubicin are chemotherapies approved for these patients. The toxicities of these chemotherapies are significant and survival when treated with these regimens is minimal. The programmed death-1 (PD-1) inhibitors nivolumab and pembrolizumab are unlikely to be effective for patients who develop progressive disease on first-line chemoimmunotherapy. Newer systemic therapies (e.g., lurbinectedin and temozolomide plus poly-ADP ribose polymerase inhibition) have demonstrated greater response rates than topotecan, amrubicin or PD-1 inhibitors. The data on these newer systemic therapies and other agents that may soon enter clinic are reviewed in this manuscript. Additionally, some of the key questions arising following clinical trials of these newer agents are highlighted.
PubMed: 33209465
DOI: 10.21037/jtd.2020.03.67 -
Case Reports in Urology 2020A 42-year-old man visited a community hospital with chief complaints of lumbago and dyschesia. Computed tomography (CT) showed multiple lung, lymph node, and bone...
A 42-year-old man visited a community hospital with chief complaints of lumbago and dyschesia. Computed tomography (CT) showed multiple lung, lymph node, and bone metastases and the irregular enlarged prostate with urinary bladder invasion. Serum prostate-specific antigen (PSA) was 544.0 ng/mL. Histological evaluation showed adenocarcinoma with the Gleason score 5 + 4, and the clinical stage was T4N1M1c as an initial diagnosis. Although androgen deprivation therapy was performed immediately, he had castration-resistant PCa after 3 months. Therefore, he received 6 courses of docetaxel chemotherapy every 3 weeks. Serum PSA was decreased to 0.2 ng/mL, and multiple metastases and prostate size were obviously reduced based on CT. He underwent robot-assisted radical prostatectomy and radiation therapy for prostatic fossa and multiple metastases. Although serum PSA level remained low, CT showed multiple liver metastases after 3 years from surgery. He received the combination therapy of cisplatin and etoposide (PE) every 4 weeks. Liver metastases had complete response. However, he visited our hospital with complaint of vomiting and a right drooping eyelid after 6 weeks from withdrawal of PE therapy. T2-weighted magnetic resonance imaging revealed multiple leptomeningeal metastases (LM). He received RT for the brain and was administered amrubicin. However, he died of PCa after 6 weeks from the diagnosis of LM.
PubMed: 33005471
DOI: 10.1155/2020/5627548 -
Hinyokika Kiyo. Acta Urologica Japonica Sep 2020A 74-year-old man presented with further treatment for muscle invasive small cell carcinoma of the bladder. After three courses of neoadjuvant chemotherapy with...
A 74-year-old man presented with further treatment for muscle invasive small cell carcinoma of the bladder. After three courses of neoadjuvant chemotherapy with cisplatine + etoposide (EP), total cystectomy was performed. The pathological findings revealed small cell carcinoma of the bladder (ypT2N0M0). Eleven months after the operation, thoracoabdominal computed tomography (CT) showed right pelvic lymph node metastasis. He underwent 9 courses of EP chemotherapy, and everolimus, finally, Amrubicin was administered. Amrubicin might be useful for small cell carcinoma of the bladder.
Topics: Aged; Carcinoma, Small Cell; Cystectomy; Etoposide; Humans; Male; Urinary Bladder Neoplasms
PubMed: 32988169
DOI: 10.14989/ActaUrolJap_66_9_313 -
Journal of Cancer Research and... 2020The benefits of second-line chemotherapy on the overall survival (OS) of small-cell lung cancer (SCLC) patients might be confounded by subsequent therapies. In this...
BACKGROUND
The benefits of second-line chemotherapy on the overall survival (OS) of small-cell lung cancer (SCLC) patients might be confounded by subsequent therapies. In this study, we aimed to determine the influence of progression-free survival (PFS) and postprogression survival (PPS) on OS after second-line chemotherapy in patients with refractory SCLC treated with amrubicin monotherapy.
MATERIALS AND METHODS
We analyzed the data of 35 patients with refractory SCLC who were treated with amrubicin monotherapy as second-line chemotherapy between July 2005 and December 2015. The correlations of PFS and PPS with OS were statistically analyzed at the individual level using Spearman's rank correlation and linear regression analyses.
RESULTS
The correlation between PPS and OS was strong (r = 0.88, P < 0.05, R = 0.87), while that between PFS and OS was weak (r = 0.60, P < 0.05, R = 0.15). The number of regimens administered after disease progression postsecond-line chemotherapy was significantly associated with PPS (P = 0.003).
CONCLUSIONS
OS is more strongly linked to PPS than to PFS in refractory SCLC patients who undergo amrubicin monotherapy as a second-line treatment. These results suggest that treatments administered after second-line chemotherapy affect the OS of refractory SCLC patients treated with amrubicin monotherapy.
Topics: Aged; Anthracyclines; Antineoplastic Agents; Disease Progression; Drug Resistance, Neoplasm; Female; Humans; Lung Neoplasms; Male; Middle Aged; Progression-Free Survival; Prospective Studies; Retrospective Studies; Small Cell Lung Carcinoma; Survival Rate
PubMed: 32930116
DOI: 10.4103/jcrt.JCRT_1170_16 -
Cancer Management and Research 2020Amrubicin (AMR) is an anticancer drug for patients with relapsed small-cell lung cancer (SCLC). However, the efficacy of AMR in elderly patients with relapsed SCLC after...
PURPOSE
Amrubicin (AMR) is an anticancer drug for patients with relapsed small-cell lung cancer (SCLC). However, the efficacy of AMR in elderly patients with relapsed SCLC after chemotherapy by carboplatin plus etoposide (CE) has not been sufficiently evaluated.
PATIENTS AND METHODS
The medical records of patients with relapsed SCLC who received AMR as second-line chemotherapy were retrospectively reviewed, and their treatment outcomes were evaluated.
RESULTS
Forty-one patients with a median age of 76 years were analyzed. The overall response rate was 26.8%. Median progression-free survival (PFS) and overall survival (OS) were 3.5 and 8.1 months, respectively. While the median PFS of 4.7 and 2.8 months in the sensitive relapse and the refractory relapse group differed significantly (=0.043), respectively, the median OS of 10.7 and 6.8 months in the respective relapse groups did not indicate a statistically significant difference (=0.24). The median PFS in a group with a modified Glasgow prognostic score (mGPS) of 0 and a group with a mGPS 1 or 2 were 4.5 and 1.6 months (=0.052), respectively, and the median OS in the respective mGPS groups were 10.7 and 4.4 months (=0.034). Multivariate analysis identified good performance status, limited disease, and mGPS 0 as favorable independent predictors of PFS and OS of AMR monotherapy. Grade 3 or higher neutropenia was observed in 23 patients (56%), and febrile neutropenia was observed in nine patients (22%). Non-hematological toxic effects were relatively mild, and pneumonitis and treatment-related deaths were not observed.
CONCLUSION
AMR is an effective and feasible regimen for elderly patients with relapsed SCLC after CE therapy.
PubMed: 32606979
DOI: 10.2147/CMAR.S255552 -
International Cancer Conference Journal Jul 2020Standard therapy for metastatic small cell carcinoma of the prostate (SCCP) remains undefined. We have effectively treated relapsed SCCP with amrubicin. A 72-year-old...
Standard therapy for metastatic small cell carcinoma of the prostate (SCCP) remains undefined. We have effectively treated relapsed SCCP with amrubicin. A 72-year-old patient, diagnosed with T4N1M0 prostate cancer, started hormonal therapy in May 2012, elsewhere, and his prostate-specific antigen levels remained low. However, pulmonary and hepatic metastases occurred; high neuron-specific enolase levels suggested SCCP, which was confirmed by repeated biopsy at our institution. In October 2016, chemotherapy with irinotecan and cisplatin was initiated for metastases to the lung, liver, and left pelvic lymph nodes, and partial response (PR) was achieved. After six cycles, brain metastases occurred. After ten cycles, his pro-gastrin-releasing peptide levels increased suddenly, and brain and hepatic metastases enlarged. Amrubicin was started in December 2016 and seven cycles were safely completed, with PR and markedly reduced brain metastasis volume, until his pneumonitis-related death in June 2017. Amrubicin may be an effective second-line chemotherapy option for SCCP.
PubMed: 32582522
DOI: 10.1007/s13691-020-00416-4